An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings

Background. In the Irbesartan in Diabetic Nephropathy Trial (IDNT), treatment with irbesartan demonstrated 23 and 20% reductions in the combined endpoint of doubling of serum creatinine (DSC), end-stage renal disease (ESRD) or death in patients with hypertension, type 2 diabetes and overt nephropathy compared with amlodipine and control, respectively. A simulation model was developed to project long-term cost consequences of the IDNT in Belgium and France. Methods. A Markov model simulated progression from nephropathy to DSC, ESRD and death in patients with hypertension, type 2 diabetes and overt nephropathy. Treatment-specific probabilities were derived from IDNT. Country-specific ESRD-related data were retrieved from published sources. Delay in onset of ESRD, life expectancy and mean lifetime costs were calculated for patients with a baseline age of 59 years. Future costs were discounted at 3% per annum (p.a.), and clinical benefits were discounted at 0 and 3% p.a.. Extensive sensitivity analyses were performed. Results. Onset of ESRD was delayed with irbesartan by 1.41 and 1.35 years vs amlodipine and control, respectively. When a 10-year time horizon was considered, delay in ESRD onset led to anticipated improvements in life expectancy of 0.13 years vs amlodipine and 0.26 years vs control. Irbesartan was associated with cost savings of €14 949 and €9205/patient in Belgium, and €20 128 and €13 337 in France, vs amlodipine and control, respectively. The results were robust under a wide range of plausible assumptions. Conclusions. Treating patients with hypertension, type 2 diabetes and overt nephropathy using irbesartan was both cost- and life-saving compared with amlodipine and contro

Further insights into the floral character of Touriga Nacional Wines

Higher-quality Touriga Nacional (TN) wines are characterized by a fruity-citric aroma described as sweet and fresh citrus evoking the bergamot fruit (Citrus bergamia). In fact, “bergamot-like” descriptor is currently employed to rate higher quality TN wines. The aim of thiswork was to identify among volatile compounds present in bergamot fruit extracts (mainly terpenes) which of them contributes the most to the bergamot overall perception, and relate these data with the volatile composition of TN wines. The identification of the most important descriptors was done by sensory analysis. Among 18 descriptors 3were selected: bergamot-like aroma, orange like, and violet. A GCO of a typical TN wine extract allows the identification of 3 related odorant zones ZO1, ZO2, and ZO3 related with bergamot-like aroma. Using AEDA, ZO2 was confirmed to be one of the most important odorant zones. Using AEDA the presence of linalool and linalyl acetate was confirmed. A similarity test was performedwith a non-TN wine added with linalool and linalyl acetate alone or in combinations. The highest similarity value was observed when linalool (SV = 5.9) was added. In fact, results obtained from the analysis of several red wines from different varieties show that terpenols are present in higher amounts in wines coming from TN variety, which proves that these compounds can be the clue to the varietal aroma of TN wines

Photomorphogenic mutants of tomato

Photomorphogenesis of tomato is being studied with the aid of mutants which are either modified in their photore- ceptor composition or in their signal transduction chain(s) . Several mutants affecting the phytochrome family of photoreceptors, some of which appear deficient for specific genes encoding phytochrome apoproteins have been isolated . In addition, other mutants, including transgenic lines overexpressing phytochrome A, exhibit exaggerated photomorphogenesis during de-etiolation . Anthocyanin biosynthesis and plastid development are being used as model systems for the dissection of the complex interactions among photomorphogenic photoreceptors and to elucidate the nature of their transduction chains

The Unusual Monomer Recognition of Guanine-Containing Mixed Sequence DNA by a Dithiophene Heterocyclic Diamidine

DB1255 is a symmetrical diamidinophenyl-dithiophene that exhibits cellular activity by binding to DNA and inhibiting binding of ERG, an ETS family transcription factor that is commonly overexpressed or translocated in leukemia and prostate cancer [Nhili, R., Peixoto, P., Depauw, S., Flajollet, S., Dezitter, X., Munde, M. M., Ismail, M. A., Kumar, A., Farahat, A. A., Stephens, C. E., Duterque-Coquillaud, M., Wilson, W. D., Boykin, D. W., and David-Cordonnier, M. H. (2013) Nucleic Acids Res. 41, 125−138]. Because transcription factor inhibition is complex but is an attractive area for anticancer and antiparasitic drug development, we have evaluated the DNA interactions of additional derivatives of DB1255 to gain an improved understanding of the biophysical chemistry of complex function and inhibition. DNase I footprinting, biosensor surface plasmon resonance, and circular dichroism experiments show that DB1255 has an unusual and strong monomer binding mode in minor groove sites that contain a single GC base pair flanked by AT base pairs, for example, 5′-ATGAT-3′. Closely related derivatives, such as compounds with the thiophene replaced with furan or selenophane, bind very weakly to GC-containing sequences and do not have biological activity. DB1255 is selective for the ATGAT site; however, a similar sequence, 5′-ATGAC-3′, binds DB1255 more weakly and does not produce a footprint. Molecular docking studies show that the two thiophene sulfur atoms form strong, bifurcated hydrogen bond-type interactions with the G-N-H sequence that extends into the minor groove while the amidines form hydrogen bonds to the flanking AT base pairs. The central dithiophene unit of DB1255 thus forms an excellent, but unexpected, single-GC base pair recognition module in a monomer minor groove complex

The influence of cycloplegic in objective refraction

The purpose of this study was to compare refractions measured with an autorefractor and retinoscopy in cycloplegic and non-cycloplegic eyes. The objective refractions were performed in 199 right eyes from 199 healthy young adults with a mean age of 21.6 ±2.66 years. The measurements were performed first without cycloplegia and repeated 30 minutes later with cycloplegia. Data were analyzed using Fourier decomposition of the power profile. More negative values of component M and J0 were give by non-cycloplegic autorefraction compared to cycloplegic autorefraction (p<0.001). However more positive values were given by non-cycloplegic autorefraciton regarding to the J45 vector, althought this differences were not statistically significant (p=0.233). Regarding retinoscopy, more negative values of component M where obtained with non-cycloplegic retinoscopy (p<0.001); for the cylindrical vectors J0 and J45 the retinoscopy without cycloplegic yields more negative values (p= 0.234; p= 0.112, respectively). Accepting that differences between cycloplegic and non-cycloplegic retinoscopy are only due to accommodative response, present results confirm that when performed by an experienced clinician, retinoscopy is a more reliable method to obtain objective start point for refraction under non-cycloplegic conditions

Cerebral microbleeds a guide to detection and interpretation

Cerebral microbleeds (CMB) are increasingly recognized neuroimaging findings, occurring with cerebrovascular disease, dementia, and normal aging. Recent years have seen substantial progress, particularly in developing newer MRI methodologies for CMB detection and applying them to population-based elderly samples. This review focuses on these recent developments and their impact on two major questions: how CMB are detected, and how they should be interpreted. There is now ample evidence that prevalence and number of detected CMB varies with MRI characteristics such as pulse sequence, sequence parameters, spatial resolution, magnetic field strength, and post-processing, underlining the importance of MRI technique in interpreting studies. Recent investigations using sensitive techniques find the prevalence of CMB detected in community-dwelling elderly to be surprisingly high. We propose procedural guidelines for identifying CMB and suggest possible future approaches for elucidating the role of these common lesions as markers for, and potential contributors to, small vessel brain disease

Clinical, Neuroimaging, and Genetic Markers in Cerebral Amyloid Angiopathy-Related Inflammation: A Systematic Review and Meta-Analysis

Background: There are limited data regarding the prevalence of distinct clinical, neuroimaging and genetic markers among patients diagnosed with cerebral amyloid angiopathy-related inflammation (CAA-ri). We sought to determine the prevalence of clinical, radiological, genetic and cerebrospinal fluid biomarker findings in patients with CAA-ri. Methods: A systematic review and meta-analysis of published studies including patients with CAA-ri was conducted to determine the prevalence of clinical, neuroimaging, genetic and cerebrospinal fluid biomarker findings. Subgroup analyses were performed based on (1) prospective or retrospective study design and (2) CAA-ri diagnosis with or without available biopsy. We pooled the prevalence rates using random-effects models and assessed the heterogeneity using Cochran-Q and I2-statistics. Results: We identified 4 prospective and 17 retrospective cohort studies comprising 378 patients with CAA-ri (mean age, 71.5 years; women, 52%). The pooled prevalence rates were as follows: cognitive decline at presentation 70% ([95% CI, 54%-84%]; I2=82%), focal neurological deficits 55% ([95% CI, 40%-70%]; I2=82%), encephalopathy 54% ([95% CI, 39%-68%]; I2=43%), seizures 37% ([95% CI, 27%-49%]; I2=65%), headache 31% ([95% CI, 22%-42%]; I2=58%), T2/fluid-attenuated inversion recovery-hyperintense white matter lesions 98% ([95% CI, 93%-100%]; I2=44%), lobar cerebral microbleeds 96% ([95% CI, 92%-99%]; I2=25%), gadolinium enhancing lesions 54% ([95% CI, 42%-66%]; I2=62%), cortical superficial siderosis 51% ([95% CI, 34%-68%]; I2=77%) and lobar macrohemorrhage 40% ([95% CI, 11%-73%]; I2=88%). The prevalence rate of the ApoE (Apolipoprotein E) ϵ4/ϵ4 genotype was 34% ([95% CI, 17%-53%]; I2=76%). Subgroup analyses demonstrated no differences in these prevalence rates based on study design and diagnostic strategy. Conclusions: Cognitive decline was the most common clinical feature. Hyperintense T2/fluid-attenuated inversion recovery white matter lesions and lobar cerebral microbleeds were by far the most prevalent neuroimaging findings. Thirty-four percent of patients with CAA-ri have homozygous ApoE ϵ4/ϵ4 genotype and scarce data exist regarding the cerebrospinal fluid biomarkers and its significance in these patients

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD